Abstract Glaucoma is a leading cause of irreversible blindness worldwide, affecting over 2.2 million Americans. With an aging population, it is estimated that by 2020 the number of people suffering glaucoma will reach 80 million worldwide, with 11 bilaterally blind. The goal of this study is to develop a novel tool for imaging and measuring elastic properties of the optic nerve head (ONH) and lamina cribrosa (LC) non-invasively. To address this goal, we propose to use phase-resolved OCT to detect small displacements induced by acoustic radiation force (ARF) in the ONH. We further propose to build a novel single crystal 2D array operating in the 4~10 MHz range to generate the ARF pushing force. We propose to use single crystal ultrasound transducers for increased sensitivity. The combined system will enable us to generate images depicting local displacements with nanometer resolution. Using state-of-the-art numerical models this data will be integrated with the complex tissue macro and microstructure to determine the anisotropic, inhomogeneous elastic properties of the tissues of the ONH with high resolution and sensitivity. This will allow us to characterize in detail the association between age, race and gender on the mechanical properties of the tissues of the ONH. Our Specific Aims are: Specific Aim 1: Develop single crystal 2D ultrasound array for ARF pushing force generation. Specific Aim 2: Develop an integrated 2D array ARF-Optical coherence elastography (OCE) system that enables coregistered OCT, US, and ARF-OCE imaging. Specific Aim 3: Develop and validate numerical models that integrate the experimental data from Aims 1 and 2 to determine the local mechanical properties of the LC and ONH. Specific Aim 4: Conduct ex-vivo elastography of human cadaveric and rabbit eyes to establish the capability and assess the performance of the ARF-OCE system to detect changes in ONH and LC tissue properties associated with age, gender and species. In human eyes, we will also determine differences due to race or disease and between regions of the ONH. Specific Aim 5: Demonstrate preclinical imaging capability with in-vivo imaging of LC and ONH in rabbit eyes using ARF-OCE system and optimize system for in-vivo imaging.